A phase Ib/II dose expansion study of subcutaneous sasanlimab in patients with locally advanced or metastatic non-small-cell lung cancer and urothelial carcinoma.

BACKGROUND: Sasanlimab is an antibody to the programmed cell death protein 1 receptor. We report updated data of subcutaneous sasanlimab in non-small-cell lung cancer (NSCLC) and urothelial carcinoma dose expansion cohorts from a first-in-human phase Ib/II study. PATIENTS AND METHODS: Patients were ≥18 years of age with NSCLC or urothelial carcinoma, and no prior immunotherapies, who progressed on or were intolerant to systemic therapy, or for whom systemic therapy was refused or unavailable. Patients received subcutaneous sasanlimab at 300 mg every 4 weeks (q4w). Primary objectives were to evaluate safety, tolerability, and clinical efficacy by objective response rate (ORR). RESULTS: Sixty-eight and 38 patients with NSCLC and urothelial carcinoma, respectively, received subcutaneous sasanlimab. Overall, sasanlimab was well tolerated; 13.2% of patients experienced grade ≥3 treatment-related adverse events. Confirmed ORR was 16.4% and 18.4% in the NSCLC and urothelial carcinoma cohorts, respectively. ORR was generally higher in patients with high programmed death-ligand 1 (PD-L1) expression (≥25%) and high tumor mutational burden (TMB; >75%). In the NSCLC and urothelial carcinoma cohorts, median progression-free survival (PFS) was 3.7 and 2.9 months, respectively; corresponding median overall survival (OS) was 14.7 and 10.9 months. Overall, longer median PFS and OS correlated with high PD-L1 expression and high TMB. Longer median PFS and OS were also associated with T-cell inflamed gene signature in the urothelial carcinoma cohort. CONCLUSIONS: Subcutaneous sasanlimab at 300 mg q4w was well tolerated with promising clinical efficacy observed. Phase II and III clinical trials of sasanlimab are ongoing to validate clinical benefit. Subcutaneous sasanlimab may be a potential treatment option for patients with NSCLC or urothelial carcinoma.

Outcomes of surgery for dermatofibrosarcoma protuberans.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue sarcoma usually presenting as nodular cutaneous mass on the trunk and proximal extremity. The tumour grows slowly, typically over years. The standard treatment is wide local excision with at least a 3-cm margin. The local regional recurrence is up to 50%, emphasizing the need for wide margins for local control. A small fraction of DFSP may metastasize, but on histological examination such tumours have features of fibrosarcomas rather than DFSP. HYPOTHESIS: This study was done to review our experience of the time interval to recurrence of DFSP. DESIGN: A retrospective review was undertaken to identify patients with DFSP in our university teaching hospital. METHODS: All patients received their primary surgical treatment in our department between February 1968 and June 2001. Treatment consisted of wide local excision with margins of at least 3 cm. The chi-square test and Fisher's exact test were performed to determine the relationship between recurrence and clinicopathological variables. We evaluated the prognostic variables using the Kaplan-Meier method with log-rank comparison. RESULTS: The median follow-up period was 59 months. The 5 and 10-year disease-free survival (DFS) were 86 and 76%, respectively. The overall recurrence rate was 16.7%. The mean time to recurrence was 38+/-12 months (range 1-100 months). In 30% of those patients with recurrences, the local regional recurrence was after 5 years. CONCLUSION: Wide local excision with good margins decreases local regional recurrences in patients with DFSP. Close surveillance is necessary even beyond 5 years because late recurrences occur.

Gamma probe-directed lymphatic mapping and sentinel lymphadenectomy in primary melanoma: Reliability of the procedure and analysis of failures after long-term follow-up.

BACKGROUND AND OBJECTIVES: Some patients presenting with cutaneous malignant melanoma without palpable adenopathy have regional metastatic disease. The results of a prospective clinical study of gamma probe-directed sentinel lymph node (SLN) biopsy are presented. METHODS: Over a 3-year period, 103 patients with a diagnosis of invasive primary cutaneous malignant melanoma (Breslow > 0.12 mm or > Clark level II) underwent preoperative lymphoscintigraphy with technetium sulfur colloid followed by gamma-probe-guided sentinel lymphadenectomy. There were 46 women and 57 men with a mean age of 55.7 years (range, 19-91). RESULTS: Mean Breslow thickness was 2.3 mm (range, 0.12-10 mm). Primary locations were head and neck in 12, trunk 46, upper extremity 19, and lower extremity in 26. One hundred sixteen lymph node basins were mapped in 103 patients. Axillary, inguinal, and cervical nodal basins comprised 55, 34, and 11% of the total basins evaluated, respectively. Sixty-eight patients (66%) underwent lymphatic mapping of one regional nodal basin, 27 patients (26%) underwent synchronous lymphatic mapping of 2 regional nodal basins, 6 patients (6%) underwent synchronous lymphatic mapping of 3 regional nodal basins, and 2 patients (2%) underwent synchronous lymphatic mapping of 4 regional nodal basins. Seroma or infection did not occur in any patients. Micrometastatic disease was identified in 15 sentinel lymph node biopsy sites in 13 (10%) patients. Of 10 patients undergoing lymph node dissection, 9(90%) had no additional pathological lymph node involvement. We achieved 99% success rate, 1% rate of failed sentinel node procedure, and 8% false-negative rate after median follow-up for 2 years. CONCLUSIONS: We concluded that gamma probe-directed sentinel lymph node biopsy is a straightforward procedure which can be done in the outpatient setting and facilitates management of patients with cutaneous malignant melanoma. It allows the surgeon to identify all basins at risk for metastatic disease and the location of the sentinel node(s) in relation to the basin.

Nonoperative management of blunt splenic and hepatic trauma in the pediatric population: significant differences between adult and pediatric surgeons?

Although operative management was the preferred method of treating blunt abdominal trauma in the past, recent literature and practice recommend a nonsurgical approach to most pediatric splenic and hepatic injuries. The majority of data supporting the safety and efficacy of this nonoperative approach are derived from university trauma programs with a pediatric center where care was managed by pediatric surgeons only. To evaluate the applicability of this approach in a regional trauma center where pediatric patients are managed by pediatric and non-pediatric surgeons we reviewed the experience at a Level II community trauma center. Fifty-four children (16 years of age or less) were admitted between April 1992 and April 1998 after sustaining blunt traumatic splenic and/or hepatic injuries. There were 37 (69%) males and 17 (31%) females; the average age was 11 years (range 4 months to 16 years). Of the 54 patients 34 (63%) sustained splenic injuries, 17 (31%) sustained hepatic injuries, and three (6%) sustained both splenic and hepatic injuries. All of these injuries were diagnosed by CT scan or during laparotomy. The average Injury Severity Score was 14.9 with a range from four to 57. Of the 47 patients initially admitted for nonoperative management one patient failed nonoperative management and required operative intervention. In our study 98 per cent (46 of 47 patients) of pediatric patients were successfully managed nonoperatively. Complications of nonoperative management occurred in two patients. Both developed splenic pseudocysts after splenic injury, which required later operative repair. These data are comparable with those from university trauma programs and confirm that nonoperative management is safe in a community trauma center. The majority of children with blunt splenic and hepatic trauma can be successfully treated without surgery, in a regional trauma center treated by nonpediatric trauma surgeons, if the decision is based on careful initial evaluation, aggressive resuscitation, and close observation of their hemodynamic stability.

Advanced breast biopsy instrumentation (ABBI) and management of nonpalpable breast abnormalities: a community hospital experience.

A range of diagnostic techniques have been in use for determining the nature of non-palpable mammographic abnormalities over the last decade, these include stereotactic and ultrasound guided cytology, core biopsy and vacuum assisted core biopsy techniques as well as open surgical breast biopsy. Recently, a less invasive alternative has been investigated; the Advanced Breast Biopsy Instrumentation (ABBI) technique (U.S. Surgical Corporation, Norwalk, CT). ABBI employs computer-guided stereotactic localization to target and excise mammographic lesions under local anesthesia, without the need for an operating theatre. We conducted a prospective review of all cases involving the use of the ABBI system during the first 17 months' of its use in a community hospital. One hundred and twenty six patients were referred for an ABBI procedure. One hundred fourteen ABBI procedures were performed on 113 patients (average age, 53 years; range, 33-82). The lesion was removed successfully in 113 of the 114 cases. Of the 114 lesions removed with the ABBI system, 88 were microcalcifications and 26 were masses. Cancer was diagnosed in 21 patients (18%). Of the patients who had carcinoma, 11 (52%) had ductal carcinoma in situ, 9 (43%) had infiltrating ductal carcinoma, and 1 (5%) had infiltrating lobular carcinoma. Postprocedural complications occurred in 7 patients (6%); 4 had small haematomas, 2 had superficial wound infections, and 1 had an abscess. We conclude that the ABBI system, is an excellent alternative (to open biopsy after needle localization or large-core biopsy) for nonpalpable breast abnormalities. It has a relatively low complication rate and should be considered as part of the surgical armamentarium for the diagnosis of indeterminate nonpalpable mammographic lesions.

Cost savings associated with changes in routine laboratory tests ordered for victims of trauma.

Not all trauma victims evaluated by the trauma service require a full complement of laboratory tests upon admission. This study set out to determine the cost savings and safety of limited laboratory testing of trauma victims. Before 1998, our admission trauma protocol included 11 laboratory tests for all trauma victims. In 1998, we created two categories: Trauma Blue--severe injury likely (Glasgow Coma Score <13; systolic blood pressure <100 mm Hg at any time; significant head, chest, abdominal, or proximal long bone injury; or clinical suspicion of need for operative or intensive care unit management) and Trauma Yellow--severe injury unlikely. The triage decision was made by the team leader or attending physician. Trauma Blue laboratory tests included an arterial blood gas, blood alcohol, type and screen or crossmatch, and urine dipstick. All patients who did not meet Trauma Blue criteria were entered in the Trauma Yellow group. There were only two tests for the Trauma Yellow group, a venous blood gas and blood alcohol. All arterial and venous blood gases measured pH, pO2, pCO2, HCO3, base deficit, hemoglobin, sodium, potassium, and ionized calcium. Other laboratory tests were done if requested by the trauma team leader or attending physician. All trauma admissions for a 3-month period were entered into this prospective study. The admitting trauma surgeon was surveyed after each admission to evaluate any problems in patient care. The test group was compared with a historical control of 100 consecutive patients under the original laboratory trauma protocol. One hundred and forty-eight (148) patients were entered into the study. Average laboratory cost per patient was $29.82 less with the study protocol. No patient care problem was identified. A cost savings of $29.82 per patient or $20,000.00 a year was realized for our institution, with no change in the quality of patient care. Trauma protocols designed to reflect a patient's potential for serious injury can result in a significant cost savings while preserving patient safety.

Angiomatoid fibrous histiocytoma: a case report and review of the literature.

We describe the case of a 5-year-old boy found to have an enlarging mass of the posterior neck. The patient underwent an uneventful excision of the mass, and pathologic examination revealed it to be an angiomatoid fibrous histiocytoma. This case report presents a review of the recent literature of this rare soft tissue tumor.

Adrenal leiomyoma: a case report and review of the literature.

We describe a case of a 65-year-old Caucasian woman found to have an enlarging mass of the left adrenal gland. Laboratory examination revealed the mass to be nonfunctional. The patient underwent an uneventful left adrenalectomy. Pathological examination revealed the mass to be a leiomyoma. These tumors are benign and develop from smooth muscle cells. They can occur in any part of the body where smooth muscular layers exist, but occur frequently in the uterus and gastrointestinal tract. This case report presents a review of the recent literature on this rare entity.